Dental pulp mesenchymal stem/stromal cells labeled with iron sucrose release exosomes and cells applied intra-nasally migrate to intracerebral glioblastoma

We report on a simple iron oxide (Venofer) labeling procedure of dental pulp mesenchymal stem cells (DP-MSCs) and DP-MSCs transduced with yeast cytosinedeaminase::uracilphosphoribosyltransferase (yCD::UPRT-DP-MSCs). Venofer is a drug approved for intravenous application to treat iron deficiency anem...

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Bibliographic Details
Published in:Neoplasma 2016, Vol.63 (6), p.925-933
Main Authors: Altanerova, U, Benejova, K, Altanerova, V, Tyciakova, S, Rychly, B, Szomolanyi, P, Ciampor, F, Cihova, M, Repiska, V, Ondicova, K, Mravec, B, Altaner, C
Format: Article
Language:English
Subjects:
Administration, Intranasal
Cell Movement
Cell Proliferation
Dental Pulp - cytology
Exosomes
Ferric Oxide, Saccharated - pharmacokinetics
Glioblastoma
Humans
Mesenchymal Stem Cells
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Summary:We report on a simple iron oxide (Venofer) labeling procedure of dental pulp mesenchymal stem cells (DP-MSCs) and DP-MSCs transduced with yeast cytosinedeaminase::uracilphosphoribosyltransferase (yCD::UPRT-DP-MSCs). Venofer is a drug approved for intravenous application to treat iron deficiency anemia in patients. Venofer labeling did not affect DP-MSCs or yCD::UPRT-DP-MSCs viability and growth kinetics. Electron microscopy of labeled cells showed internalized Venofer nanoparticles in endosomes. MRI relativity measurement of Venofer labeled DP-MSCs in a phantom arrangement revealed that 100 cells per 0.1 ml were still detectable. DP-MSCs or yCD::UPRT-DP-MSCs and the corresponding Venofer labeled cells release exosomes into conditional medium (CM). CM from yCD::UPRT-DP-MSCs in the presence of a prodrug 5-fluorocytosine caused tumor cell death in a dose dependent manner. Iron labeled DP-MSCs or yCD::UPRT-DP-MSCs sustained their tumor tropism in vivo; intra-nasally applied cells migrated and specifically engrafted orthotopic glioblastoma xenografts in rats.
ISSN:0028-2685
DOI:10.4149/neo_2016_611